Brohem C A, Sawada T C H, Massaro R R, Almeida R L, Rivelli D P, Ropke C D, da Silva V V, de Lima T M, Curi R, Barros S B M, Maria-Engler S S
Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, Brazil.
Toxicol In Vitro. 2009 Feb;23(1):111-9. doi: 10.1016/j.tiv.2008.11.004. Epub 2008 Nov 24.
Pothomorphe umbellata, a native Brazilian plant, is popularly known to be effective in the treatment of skin lesions. This benefit is attributed to 4-nerolidylcatechol (4-NC), a compound extracted from P. umbellata. Since melanomas show prominent resistance to apoptosis and exhibit extreme chemoresistance to multiple forms of therapy, novel compounds addressing induction of cell death are worth investigating. Here, we evaluated effects on cell cycle progression and possible cytotoxic activity of 4-NC in melanoma cell lines as well as human dermal fibroblasts. Inhibitory effects on cell invasion and MMP activity were also investigated. 4-NC showed cytotoxic activity for all melanoma cell lines tested (IC50=20-40 microM, 24h for tumoral cell lines; IC50=50 microM for fibroblast cell line) associated with its capacity to induce apoptosis. Furthermore, this is the first time that 4-NC is described as an inhibitor of cell invasiveness, due mainly to a G1 cell cycle arrest and inhibition of MMP-2 activity in melanoma cell lines.
伞形波托木是一种原产于巴西的植物,人们普遍认为它对治疗皮肤损伤有效。这种益处归因于从伞形波托木中提取的一种化合物4-橙花叔基儿茶酚(4-NC)。由于黑色素瘤对细胞凋亡具有显著抗性,并且对多种治疗形式表现出极强的化疗耐药性,因此研究能够诱导细胞死亡的新型化合物具有重要意义。在此,我们评估了4-NC对黑色素瘤细胞系以及人皮肤成纤维细胞的细胞周期进程和可能的细胞毒性活性的影响。我们还研究了其对细胞侵袭和基质金属蛋白酶(MMP)活性的抑制作用。4-NC对所有测试的黑色素瘤细胞系均表现出细胞毒性活性(肿瘤细胞系24小时的IC50 = 20 - 40微摩尔;成纤维细胞系的IC50 = 50微摩尔),这与其诱导细胞凋亡的能力相关。此外,这是首次将4-NC描述为细胞侵袭的抑制剂,主要是因为它能使黑色素瘤细胞系的细胞周期停滞在G1期并抑制MMP-2活性。